title: Traction forces exerted by epithelial cell sheets.
abstract: Whereas the adhesion and migration of individual cells have been well described in terms of physical forces, the mechanics of multicellular assemblies is still poorly understood. Here, we study the behavior of epithelial cells cultured on microfabricated substrates designed to measure cell-to-substrate interactions. These substrates are covered by a dense array of flexible micropillars whose deflection enables us to measure traction forces. They are obtained by lithography and soft replica molding. The pillar deflection is measured by video microscopy and images are analyzed with home-made multiple particle tracking software. First, we have characterized the temporal and spatial distributions of traction forces of cellular assemblies of various sizes. The mechanical force balance within epithelial cell sheets shows that the forces exerted by neighboring cells strongly depend on their relative position in the monolayer: the largest deformations are always localized at the edge of the islands of cells in the active areas of cell protrusions. The average traction stress rapidly decreases from its maximum value at the edge but remains much larger than the inherent noise due to the force resolution of our pillar tracking software, indicating an important mechanical activity inside epithelial cell islands. Moreover, these traction forces vary linearly with the rigidity of the substrate over about two decades, suggesting that cells exert a given amount of deformation rather than a force. Finally, we engineer micropatterned substrates supporting pillars with anisotropic stiffness. On such substrates cellular growth is aligned with respect to the stiffest direction in correlation with the magnitude of the applied traction forces.
authors.affiliation: Laboratoire Matière et Systèmes Complexes (MSC), UMR CNRS 7057 and Université Paris Diderot, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Saez
authors.forename: E
authors.initials: E
authors.lastname: Anon
authors.forename: M
authors.initials: M
authors.lastname: Ghibaudo
authors.forename: O
authors.initials: O
authors.lastname: du Roure
authors.forename: J-M
authors.initials: JM
authors.lastname: Di Meglio
authors.forename: P
authors.initials: P
authors.lastname: Hersen
authors.forename: P
authors.initials: P
authors.lastname: Silberzan
authors.forename: A
authors.initials: A
authors.lastname: Buguin
authors.forename: B
authors.initials: B
authors.lastname: Ladoux
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D003198:Computer Simulation; D004847:Epithelial Cells / Q000502:physiology*; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D044085:Microfluidics; D008954:Models, Biological; D033081:Shear Strength / Q000502:physiology*; D013314:Stress, Mechanical